In contrast, both anaesthetic gases (given for 60 min and without subsequent capsaicin injection) induced ERK1/2 activation in a different group of mainly lamina I neurons bilaterally. The total number of spinal dorsal horn neurons labelled on the ipsilateral side following capsaicin injection into the isoflurane-, or sevoflurane-, anaesthetised animals was significantly less than that produced by capsaicin alone. Further, capsaicin injection into isoflurane-, or sevoflurane-, anaesthetised animals reduced pERK1/2 induced by the gases alone on both sides. These key original findings are inconsistent with the suggestion that isoflurane-, or sevoflurane-, induced sensitisation of TRPV1 by capsaicin, or other agonist, is translated into induction of spinal nociceptive processing and consequential pain sensation.